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dc.contributor.authorPane, JA
dc.contributor.authorFleming, FE
dc.contributor.authorGraham, KL
dc.contributor.authorThomas, HE
dc.contributor.authorKay, TWH
dc.contributor.authorCoulson, BS
dc.date.accessioned2021-02-05T00:32:36Z
dc.date.available2021-02-05T00:32:36Z
dc.date.issued2016-07-13
dc.identifierpii: srep29697
dc.identifier.citationPane, J. A., Fleming, F. E., Graham, K. L., Thomas, H. E., Kay, T. W. H. & Coulson, B. S. (2016). Rotavirus acceleration of type 1 diabetes in non-obese diabetic mice depends on type I interferon signalling. SCIENTIFIC REPORTS, 6 (1), https://doi.org/10.1038/srep29697.
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11343/260048
dc.description.abstractRotavirus infection is associated with childhood progression to type 1 diabetes. Infection by monkey rotavirus RRV accelerates diabetes onset in non-obese diabetic (NOD) mice, which relates to regional lymph node infection and a T helper 1-specific immune response. When stimulated ex vivo with RRV, plasmacytoid dendritic cells (pDCs) from naïve NOD mice secrete type I interferon, which induces the activation of bystander lymphocytes, including islet-autoreactive T cells. This is our proposed mechanism for diabetes acceleration by rotaviruses. Here we demonstrate bystander lymphocyte activation in RRV-infected NOD mice, which showed pDC activation and strong upregulation of interferon-dependent gene expression, particularly within lymph nodes. The requirement for type I interferon signalling was analysed using NOD mice lacking a functional type I interferon receptor (NOD.IFNAR1(-/-) mice). Compared with NOD mice, NOD.IFNAR1(-/-) mice showed 8-fold higher RRV titers in lymph nodes and 3-fold higher titers of total RRV antibody in serum. However, RRV-infected NOD.IFNAR1(-/-) mice exhibited delayed pDC and lymphocyte activation, no T helper 1 bias in RRV-specific antibodies and unaltered diabetes onset when compared with uninfected controls. Thus, the type I interferon signalling induced by RRV infection is required for bystander lymphocyte activation and accelerated type 1 diabetes onset in genetically susceptible mice.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.titleRotavirus acceleration of type 1 diabetes in non-obese diabetic mice depends on type I interferon signalling
dc.typeJournal Article
dc.identifier.doi10.1038/srep29697
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.affiliation.departmentMedicine and Radiology
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleScientific Reports
melbourne.source.volume6
melbourne.source.issue1
melbourne.identifier.nhmrc1103279
melbourne.identifier.nhmrc1044868
melbourne.identifier.nhmrc628319
dc.rights.licenseCC BY
melbourne.elementsid1083195
melbourne.contributor.authorCoulson, Barbara
melbourne.contributor.authorFleming, Fiona
melbourne.contributor.authorKay, Thomas
melbourne.contributor.authorGraham, Kate
melbourne.contributor.authorNeil, Jessica
dc.identifier.eissn2045-2322
melbourne.identifier.fundernameidNHMRC, 1103279
melbourne.identifier.fundernameidNHMRC, 1044868
melbourne.identifier.fundernameidNHMRC, 628319
melbourne.accessrightsOpen Access


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